Clinical Review: Acne

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. It is characterised by seborrhoea, non-inflammatory and inflammatory lesions, and scarring.

Acne has psychological sequelae (SPL)
Acne has psychological sequelae (SPL)

Section 1: Epidemiology and aetiology

Almost all teenagers can expect some degree of acne, with moderate to severe disease in about 15% of 15- to 17-year-olds.1 Acne develops earlier in girls, but more boys are affected. Late-onset acne (>25 years) is seen in 8% of patients and significant lesions are seen in 1% of men and 5% of women at the age of 40.2

Aetiology
Genetic factors play a part. There is a high concordance between monozygotic twins and a greater risk of severity is associated with a positive family history, maternal acne being associated with the greatest risk.1,3

Acne is associated with increased insulin resistance and high serum dehydroepiandrosterone, which may explain its association with polycystic ovary syndrome (PCOS).

Abnormal androgen production is responsible for patients developing acne in Cushing's syndrome, congenital adrenal hyperplasia, patients using anabolic steroids and virilising tumours in females.

Factors that can cause acne to flare include menstruation, emotional stress, picking and smoking.4

Antiepileptic drugs are associated with a monomorphic acneiform rash and it has been suggested the severity of the acneiform eruption produced by the chemotherapy drug erlotinib may correlate with increased survival.5

There is limited evidence to support the belief that diet affects acne. Anecdotally, sunlight can improve acne and UVB phototherapy is occasionally used to treat it.

Other less common forms of acne are shown in table 1.

Four main factors involved in acne

  • Increased sebum (dependent on androgen drive or increased androgen receptor sensitivity)
  • Abnormal keratinisation
  • Colonisation of pilosebaceous duct by Propionibacterium acnes
  • Inflammation

Section 2: Making the diagnosis

Acne is a clinical diagnosis. The distribution corresponds to areas with the densest population of pilosebaceous units, such as the face (99%).

Comedones may be open (blackheads) or closed (whiteheads) and show no clinical inflammation.

Inflammatory lesions may be superficial (papules or pustules) or deep (pustules or nodules) and are raised erythematous lesions.

Nodulocystic acne is a severe form consisting of comedones, inflammatory lesions and large nodules, with a high risk of scarring.

Scarring may occur with superficial or deep lesions in scar-prone patients and may be described as ice-pick, depressed fibrotic, atrophic, hypertrophic or keloidal. Deeply pigmented skin is more susceptible to persistent postinflammatory hyperpigmentation.

Acne fulminans, a severe form, is associated with fever, arthralgia and lymphadenopathy. Acne carries a significant psychological morbidity.

When to carry out further investigations

  • PCOS in females with hirsutism or dysmenorrhoea. Bloods, including testosterone, prolactin, SHBG, LH:FSH ratio, TSH, lipids; pelvic ultrasound.
  • Prepubertal patients with signs of virilisation. Bloods, including TFTs, testosterone, dehydroepiandrosterone sulphate, androstenedione and 17-hydroxyprogesterone.
  • Skin swabs if Gram-negative folliculitis is suspected.

Section 3: Managing the condition

The treatment of acne is based on disease severity, extent and patient factors (see table 2).

Most commonly, combination treatments are used to address the comedonal and inflammatory components of the disease.

Mild acne
Topical retinoids (for example, isotretinoin, adapalene, tretinoin) are antiproliferative and are used to treat comedonal acne.

Available as gels and creams, they should be applied once or twice daily. They are recommended first-line for maintenance and can be continued indefinitely and combined with topical antibiotics or benzoyl peroxide (BPO). All retinoids are contraindicated in pregnancy.

BPO, a non-antibiotic antimicrobial agent, can be used on its own or in combination for mild acne. BPO (2.5-5% strength) should be started at a low frequency (such as three times a week) and titrated up to daily use, to reduce irritation.

Topical antibiotics, such as clindamycin and erythromycin, are commonly used, but monotherapy should be avoided to prevent resistance. They should be combined with BPO or a retinoid for best results.

Topical azelaic acid can be used alone or with a topical retinoid for mild papulopustular disease.

Moderate acne
The key to success in moderate acne is to combine treatments to treat both the comedonal and the inflammatory components.

A typical combination is an oral antibiotic with a topical retinoid and BPO. Tetracyclines are usually used first-line, in particular lymecycline and doxycycline, both of which offer the added convenience of once-daily dosing.

Minocycline is best avoided because it has a higher incidence of adverse effects compared with other tetracyclines.6 Oral erythromycin (500mg twice daily) or trimethoprim (300mg twice daily) are useful alternatives. Resistance to oral antibiotics can be minimised by using topical BPO concurrently.

In young women requiring contraception or with features of PCOS, an anti-androgenic combined oral contraceptive is recommended as part of combination therapy (either with or without an oral antibiotic), along with a topical agent.

In older women, or if estrogens need to be avoided, spironolactone is an alternative when used with contraception.7

Severe acne
In patients with severe acne, oral isotretinoin is most effective, inducing long-term remission in about 90% of cases.8 Isotretinoin significantly reduces sebum production, prevents comedone formation, reduces P acnes colonisation and is anti-inflammatory. It is usually prescribed in secondary care, owing to its side-effects and teratogenicity. Women of childbearing age must use contraception during and for at least a month after treatment.

Antibiotic resistance
Concern about antibiotic resistance has driven attempts to limit the frequency and duration of antibiotic use in acne. Resistance manifests in acne as reduced/no response or relapse after treatment. BPO is strongly bactericidal and its addition to antibiotic therapy minimises resistance at sites of application.9

UV light and laser therapy can improve inflammatory acne in the short term. Pain, erythema, swelling and hyperpigmentation are common side-effects. More comparative data and longer outcome studies are needed to define their role.9

Section 4: Prognosis

Most patients can be managed in primary care. The treatment combinations should be tried for approximately three months and their effect then assessed. Effective treatment should be continued for six months, then re-evaluated.

Patients with nodulocystic acne should be referred to secondary care for consideration of oral isotretinoin and commenced on oral antibiotic treatment in the meantime. NICE has further recommendations about referral (see section 6).

Acne usually resolves by the age of 25, but persistent disease is seen in 4% of people aged 40-49.2,7

Scarring can be more disabling than the acne itself. The best way to reduce scarring is to treat the acne early and to continue therapy for as long as necessary.

Section 5: Case study

A 12-year-old girl was brought in by her mother, who was worried that 'teenage spots' were making her daughter self-conscious and affecting her confidence.

The patient had used OTC preparations containing BPO, but with no improvement. She had no other medical conditions and had not yet reached menarche.

Examination revealed mostly closed comedones (whiteheads) on the forehead and jawline, with occasional papules on the cheeks.

Treatment was started with a combination adapalene and BPO gel, with instructions to apply it on alternate nights for two weeks before increasing to every night if tolerated. On review after two months, there was no improvement and there were more papules and some pustules present. Lymecycline 408mg daily was added to the regimen.

At the next two-month review, there was significant improvement. She was advised to continue both topical and oral treatment for a further four months. After that, there was minimal acne, although she had started menstruation and reported occasional perimenstrual spots.

She was advised to continue topical treatment and to return if she developed further papules or pustules.

Six months later she had more severe acne, which was not related to her menses. She had some early scarring on her cheeks, which was making her worried that she would have permanent scarring.

She was advised to avoid squeezing the spots and started on trimethoprim 300mg twice daily in conjunction with her adapalene/BPO gel. She was also referred to the dermatology department to consider oral isotretinoin in view of her scar risk.

When she was seen two months later in secondary care she was considered to be a suitable candidate for oral isotretinoin as she had not cleared on her second category of oral antibiotic. She was switched to oral isotretinoin monotherapy on a low dose for eight months (to minimise side-effects). This cleared her acne completely and there has been no relapse for the past two years.

Section 6: Evidence base

Guidelines

This site offers access to a range of information about acne management and prescribing, and summarises the underlying evidence.

  • Global Alliance to Improve Outcomes in Acne recommendations. Thiboutot D, Gollnick H, Bettoli V et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009; 60: S1-50.

This article provides a more in-depth review of all of the current evidence pertaining to new developments in acne management.

The authors provide some useful short summaries of the current data. There is also a succinct treatment algorithm.

Summarises information on when to refer to secondary care.

Online

Summaries of acne pathogenesis, diagnosis and treatment.

  • Goodfield MJD, Cox NH, Bowser A et al. Advice on the safe introduction and continued use of isotretinoin in acne in the UK. Br J Dermatol 2010; 162: 1172-9.

Contributed by Dr Anshoo Sahota, consultant dermatologist, Whipps Cross University Hospital and Barts and The London NHS Trust.

CPD IMPACT: EARN MORE CREDITS

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Audit patients on topical antibiotics and consider adding BPO or retinoids if needed after review.
  • Discuss a practice protocol for prescribing in acne vulgaris and agree a formulary for prescribing.
  • Review patients of childbearing age using retinoids and ensure they have been given appropriate advice about the use of contraception during their treatment.

Click here to reflect on this article and add notes to your CPD organiser on MIMS Learning

References

1. Ghodsi SZ, Orawa H, Zouboulis CC. J Invest Dermatol 2009; 129: 2136-41.

2. Cunliffe WJ, Gould DJ. BMJ 1979; 1: 1109-10.

3. Walton S, Wyatt E, Cunliffe WJ.

Br J Dermatol 1988; 18: 393-6.

4. Schafer T, Niehnaus A, Vieluf D et al. Br J Dermatol 2001; 145: 100-4.

5. Dudek A, Kmak K, Koopmeiners J et al. Lung Cancer 2006; 51(1): 89-96.

6. Garner SE, Eady EA, Popescu C et al. Cochrane Database Syst Rev 2003; 1: CD002086.

7. Perkins AC, Maglione J, Hillebrand GG et al. J Women's Health 2012; 21(2): 223-30.

8. Borghi A, Mantovani L, Minghetti S et al. J Eur Acad Dermatol Venereol 2011; 25(9): 1094-8.

9. Global Alliance to Improve Outcomes in Acne recommendations. Thiboutot D, Gollnick H, Bettoli V et al. J Am Acad Dermatol 2009; 60: S1-50.

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